Regioselective alkylation of polysubstituted imidazoles is of importance especially with regard to Angiotensin II antagonists. The mechanisms of selective alkylation are somewhat understood and can be used in some circumstances to control reaction products, i.e. the distribution of N-alkylated regioisomeric products. However, no generally applicable methods currently exist for the regloselective alkylation of these important imidazoles in quantitative yield. The product of the prior art is usually a mixture of regioisomers as shown in Scheme 1. ##STR1##
Japanese patent JP 4120063 A, Ishihara Sangyo Kaisha Ltd., describes the separation of 2-cyanoimidazole-sulphonamide derivatives by selectively hydrolyzing one of two imidazole compounds in the presence of an acid catalyst as shown in Scheme 2. This reference does not teach the selective hydrolysis of a carbon attached ester functional group. ##STR2##
No references are known that teach the regioselective hydrolysis of ester functionalized N-alkylated imidazoles.
It is apparent, as determined by the nonquantitative formation of either regioisomer during N-alkylation, and the lack of suitable methods for the large scale purification of N-alkylated imidazole that a method of purifying these very important compounds to obtain pure products from alkylation is needed.